Percorrer por autor "Costa, Rui Miguel Gil"
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- Aloysia citrodora extract as a chemopreventive agent against HPV16-induced lesions: findings from K14-HPV16 micePublication . Medeiros-Fonseca, Beatriz; Faustino-Rocha, Ana; Silva, Jessica; Silva, Mónica; Pires, Maria João; Neuparth, Maria João; Vala, Helena; Vasconcelos-Nóbrega, Cármen; Dias, Maria Inês; Barros, Lillian; Gonçalves, Lio; Gaivão, Isabel; Bastos, Margarida M.S.M.; Félix, Luís; Venâncio, Carlos; Medeiros, Rui; Costa, Rui Miguel Gil; Oliveira, Paula A.Aloysia citrodora has a long history of traditional use in treating various ailments. This study evaluated the in vivo chemopreventive efficacy and systemic toxicity of an extract of A. citrodora in a transgenic mouse model of HPV16 (human papillomavirus type 16)-induced cancer. Methods: The experiment involved six groups (n = 5): group 1 (G1, wild-type (WT), water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.013 g/mL), group 4 (G4, HPV, 0.006 g/mL), group 5 (G5, HPV, 0.008 g/mL), and group 6 (G6, HPV, 0.013 g/mL). Throughout the assay, humane endpoints, body weight, food, and water consumption were recorded weekly. The internal organs and skin of the mice were collected for analysis after they were sacrificed. Toxicological parameters that were studied included hematological and biochemical blood markers, splenic and hepatic histology, and hepatic oxidative stress. Results: A. citrodora extract seems to reduce the incidence of dysplastic and in situ carcinoma skin lesions induced by HPV16 in this model, suggesting that dietary supplementation with concentrations of 0.008 g/mL and 0.013 g/mL may have beneficial chemopreventive effects. Conclusions: The extract did not induce any concentration-dependent toxicological effects on any of the parameters included in the study, indicating a favorable toxicological profile under these experimental conditions.
- Avaliação in vivo dos efeitos fisiológicos resultantes da exposição à tíliaPublication . Macedo, Sara; Borges, Inês; Nogueira, António José M.; Barros, Lillian; Ferreira, Isabel C.F.R.; Neuparth, Maria João; Pires, Maria João; Bastos, Margarida M.S.M.; Medeiros, Rui; Costa, Rui Miguel Gil; Rosa, Eduardo; Oliveira, Paula A.O Papiloma Vírus Humano (HPV) é responsável pelo desenvolvimento do carcinoma do colo do útero, estando ainda associado a outros carcinomas. Para compreender melhor os mecanismos associados às infeções causadas por este vírus e estudar novas terapias foi desenvolvido um modelo transgénico de murganho: K14HPV16. Assim, o objetivo deste trabalho foi avaliar o efeito da administração oral do extrato hidroetanólico (80:20, v/v) de tília (Tilia platyphyllos Scop.) em murganhos machos e fêmeas K14HPV16 e wild type. Utilizaram-se 43 animais divididos em grupos de machos e fêmeas. Cada um destes grupos foi ainda dividido em dois grupos de animais K14HPV16 com e sem exposição oral à tília (4,5 mg/animal, calculado com base em trabalhos prévios feitos in vitro) e dois grupos de animais wild type com e sem tratamento. O extrato hidroetanólico foi caracterizado por HPLC-DAD-ESI/MS quanto ao perfil em compostos fenólicos e a sua estabilidade foi estudada ao longo de 5 dias consecutivos. (-)-Epicatequina, quercetina-3-O-glucósido e ácido protocatéquico, foram os compostos fenólicos maioritários identificados no extrato, estáveis durante 5 dias. Durante o ensaio experimental, com duração de 33 dias, foi registado o consumo de água, e as massas corporais individuais e consumo de comida. No final do ensaio todos os animais foram sacrificados, tendo sido recolhido sangue, para estudo bioquímico e danos oxidativos pelo ensaio dos cometas. Observou-se que o extrato de tília não provocou alterações no aspeto dos animais nem na média da massa corporal. O consumo médio de alimento foi idêntico entre grupos, os murganhos K14HPV16 consumiram mais água. Os parâmetros bioquímicos avaliados (creatinina, ureia, alanina aminotransferase e aspartato aminotransferase) não apresentaram diferenças entre grupos. Através do ensaio dos cometas não foram registados danos oxidativos entre grupos. No geral, conclui-se que a concentração de tília utilizada não apresentou efeitos adversos neste modelo animal.
- The cyclooxigenase-2 inhibitor parecoxib prevents epidermal dysplasia in HPV16-transgenic mice: efficacy and safety observationsPublication . Ferreira, Tiago; Campos, Sandra; Silva, Mónica; Ribeiro, Rita; Santos, Susana; Almeida, José L.S.; Pires, Maria João; Costa, Rui Miguel Gil; Córdova, Cláudia; Nogueira, António José M.; Neuparth, Maria João; Medeiros, Rui; Bastos, Margarida M.S.M.; Gaivão, Isabel; Peixoto, Francisco P.; Oliveira, Maria Manuel; Oliveira, Paula A.Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant e cacy, but also considerable toxicity. This study addresses the chemopreventive e ect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16+/-, n = 10, parecoxib-treated); II (HPV16+/- n = 11, untreated); III (HPV16+/-, n = 11, parecoxib-treated) and IV (HPV16+/- n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/- treated animals (0% versus 64% in HPV16+/- untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/- treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn’t modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive e ects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.
- Cytinus hypocistis (L.) L. extract effects in an animal model of papillomavirus-induced neoplasiaPublication . Medeiros, Catarina; Silva, Ana Rita; Ferreira, Tiago; Barros, Lillian; Neuparth, Maria João; Peixoto, Francisco P.; Bastos, Margarida M.S.M.; Medeiros, Rui; Costa, Rui Miguel Gil; Pires, Maria João; Faustino-Rocha, Ana; Gama, Adelina; Oliveira, Paula A.Infections with certain types of papillomavirus, such as the human papillomavirus 16 (HPV16), are associated with the development of preneoplastic lesions and cancers of the anogenital, and head and neck regions. Cytinus hypocistis (L.) L. extracts are composed of substances presenting antiproliferative, antioxidant, anti-inflammatory and antibacterial properties, which might be promising as new therapeutic compounds. This study analysed the influence of topical application of an extract obtained from C. hypocistis (CH) on K14-HPV16 and FVB/n mice to evaluate its therapeutic and toxicological properties. To achieve the study goals, 30 female mice, 33–37 weeks old, were divided into six groups (n=5/group): I (HPV+CH3.1); II (HPV+CH6.2); III (HPV+CH12.4); IV (FVB/ n+CH12.4); V (HPV+control) and VI (FVB/n+control). CH was applied topically to both ears for 28 days. After this period, all animals were sacrificed for samples collection. Skin lesions were classified histologically. Toxicological parameters included haematological and biochemical blood markers, and hepatic oxidative stress analysis. Transgenic animals showed a decrease in mean body weight regardless of the concentration of extract applied. The extract had no influence on physiological parameters, organ weight, or biochemical and oxidative stress parameters. Histology demonstrated the presence of proliferative epithelial lesions in the skin and oral mucosa of K14-HPV16 mice, with no association with the application of this extract. Overall, the application of CH extract had no influence on the skin lesions and was well tolerated by the animals in these concentrations.
- Dietary supplementation with chestnut (Castanea sativa) reduces abdominal adiposity in FVB/n mice: a preliminary studyPublication . Rodrigues, Pedro M.; Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Seixas, Fernanda; Costa, Rui Miguel Gil; Martins, Tânia; Neuparth, Maria João; Pires, Maria João; Lanzarin, Germano; Félix, Luís; Venâncio, Carlos; Ferreira, Isabel C.F.R.; Bastos, Margarida M.S.M.; Medeiros, Rui; Gaivão, Isabel; Rosa, Eduardo; Oliveira, Paula A.The production of chestnut (Castanea sativa Miller) is mostly concentrated in Europe. Chestnut is recognized by its high content of antioxidants and phytosterols. This work aimed to evaluate the e ects of dietary chestnut consumption over physiological variables of FVB/n mice. Eighteen FVB/n male 7-month-old mice were randomly divided into three experimental groups (n = 6): 1 (control group) fed a standard diet; 2 fed a diet supplemented with 0.55% (w/w) chestnut; and 3 supplemented with 1.1% (w/w) chestnut. Body weight, water, and food intake were recorded weekly. Following 35 days of supplementation, the mice were sacrificed for the collection of biological samples. Chestnut supplementation at 1.1% reduced abdominal adipose tissue. Lower serum cholesterol was also observed in animals supplemented with chestnut. There were no significant di erences concerning the incidence of histological lesions nor in biochemical markers of hepatic damage and oxidative stress. These results suggest that chestnut supplementation may contribute to regulate adipose tissue deposition.
- Efeito da aplicação repetida de Cytinus hypocistis em murganhos transgénicos (K14HPV16): avaliação de humane endpointsPublication . Medeiros-Fonseca, Beatriz; Segurado, Olga; Costa, Diana; Medeiros, Catarina; Medeiros, Rui; Pires, Maria João; Bastos, Margarida M.S.M.; Silva, Ana Rita; Barros, Lillian; Ferreira, Isabel C.F.R.; Costa, Rui Miguel Gil; Oliveira, Paula A.Em, 1959 Russel e Burch propuseram os 3Rs (Reduce, Refine e Replacement) em experimentação animal e desde então as diversas entidades envolvidas na temática têm feito esforços conjuntos para os aplicar (1). Nesse sentido foi gradualmente introduzida a avaliação e registo dos humane endpoints (HE) dos animais durante procedimentos experimentais, para monitorizar o seu sofrimento e tomar decisões sobre a necessidade, ou não, de finalizar o ensaio antes da data prevista (2). Contudo, apesar das exigências legais, observa-se grande escassez de publicações sobre a avaliação de HE nos procedimentos com animais de laboratório. Assim, é nosso objetivo com este trabalho apresentar os HE durante a aplicação diária de um creme com Cytinus hypocistis numa estirpe de murganhos transgénicos.
- Effect of hidroethanolic extract of Lavandula pedunculata (mill.) Cav. On morphometric parameters in HPV-16 trangenic micePublication . Nascimento-Gonçalves, Elisabete; Ferreira, Teresa; Moutinho, Magda S.S.; Pires, Maria João; Bastos, Margarida M.S.M.; Medeiros, Rui; Nogueira, António José M.; Barros, Lillian; Ferreira, Isabel C.F.R.; Costa, Rui Miguel Gil; Oliveira, Paula A.Lavandula penduculata (Mill.) Cav., common English name French lavender, belongs to the Lamiaceae family and has been used as a medicinal plant in infusions for respiratory and digestive systems and as a therapeutic agent with antiseptic action for cleaning wounds [1,2]. The K14HPV16 mice is a skin squamous carcinoma model that can be used to test the antitumoral properties of several chemical and natural products [3]. The aim of this work was to evaluate the effect of the hydroethanolic French lavender extract (FLE) on body weight, relative organs weights, food and water consumption in an HPV-16-transgenic mice model. The extract was obtained from a maceration with ethanol/water (80:20, v/v), and the phenolic composition was determined through HPLC-DAD-ESI/MS. Twenty-eight male mice were randomly divided into four groups (n=7/group) according to their genotype: group I (HPV16- control); II (HPV16- FLE); III (HPV16+ control) and IV (HPV16+ FLE). The FLE was administrated orally in drinking water at 6.8 mg/10mL/animal to animals from groups II and IV and changed every 4 days. The animals were kept under controlled conditions such as temperature, light and humidity
- Effect of hidroethanolic extract of Lavandula pedunculata (mill.) Cav. On morphometric parameters in HPV-16 trangenic micePublication . Nascimento-Gonçalves, Elisabete; Ferreira, Teresa; Moutinho, Magda S.S.; Pires, Maria João; Bastos, Margarida M.S.M.; Medeiros, Rui; Nogueira, António José M.; Barros, Lillian; Ferreira, Isabel C.F.R.; Costa, Rui Miguel Gil; Oliveira, Paula A.Lavandula penduculata (Mill.) Cav., common English name French lavender, belongs to the Lamiaceae family and has been used as a medicinal plant in infusions for respiratory and digestive systems and as a therapeutic agent with antiseptic action for cleaning wounds [1,2]. The K14HPV16 mice is a skin squamous carcinoma model that can be used to test the antitumoral properties of several chemical and natural products [3]. The aim of this work was to evaluate the effect of the hydroethanolic French lavender extract (FLE) on body weight, relative organs weights, food and water consumption in an HPV-16-transgenic mice model. The extract was obtained from a maceration with ethanol/water (80:20, v/v), and the phenolic composition was determined through HPLC-DAD-ESI/MS. Twenty-eight male mice were randomly divided into four groups (n=7/group) according to their genotype: group I (HPV16- control); II (HPV16- FLE); III (HPV16+ control) and IV (HPV16+ FLE). The FLE was administrated orally in drinking water at 6.8 mg/10mL/animal to animals from groups II and IV and changed every 4 days. The animals were kept under controlled conditions such as temperature, light and humidity
- Exploring the therapeutic potential of Quercus ilex acorn extract in papillomavirus-induced lesionsPublication . Medeiros-Fonseca, Beatriz; Faustino-Rocha, Ana; Pires, Maria João; Neuparth, Maria João; Vala, Helena; Vasconcelos-Nóbrega, Cármen; Gouvinhas, Irene; Barros, Ana Novo; Dias, Maria Inês; Barros, Lillian; Bastos, Margarida M.S.M.; Gonçalves, Lio; Félix, Luís; Venâncio, Carlos; Medeiros, Rui; Costa, Rui Miguel Gil; Oliveira, Paula A.Papillomaviruses (PVs) infections have been documented in numerous animal species across different regions worldwide. They often exert significant impacts on animal health and livestock production. Scientists have studied natural products for over half a century due to their diverse chemical composition, acknowledging their value in fighting cancer. Acorns (Quercus ilex) are believed to have several unexplored pharmacological properties. This study aimed to evaluate the in vivo safety and cancer chemopreventive activity of an infusion extract of Q. ilex in a transgenic mouse model of human PV (HPV)-16, which developed squamous cell carcinomas through a multistep process driven by HPV16 oncogenes. Q. ilex extract was prepared by heating in water at 90°C and then characterized by mass spectrometry. Phenolic compounds from this extract were administered in drinking water to female mice in three different concentrations (0.03, 0.06, and 0.09 g/mL) over a period of 28 consecutive days. Six groups (n = 6) were formed for this study: group 1 (G1, wildtype [WT], water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.09 g/mL), group 4 (G4, HPV, 0.03 g/mL), group 5 (G5, HPV, 0.06 g/ mL), and group 6 (G6, HPV, 0.09 g/mL). Throughout the experiment, humane endpoints, body weight, food intake, and water consumption were recorded weekly. Following the experimental period, all mice were sacrificed, and blood, internal organs, and skin samples were collected. Blood was used to measure glucose and microhematocrit and later biochemical parameters, such as creatinine, urea, albumin, alanine aminotransferase, and total proteins. Histological analysis was performed on skin and organ samples. The administration of Q. ilex extract resulted in a statistically significant increase in relative organ weight among HPV transgenic animals, indicating adaptive biological response to the tested concentrations. Moreover, a reduction in characteristic skin lesions was observed in animals treated with the 0.06 and 0.09 g/mL extract. These results provide a favorable chemopreventive profile for Q. ilex extract at concentrations of 0.06 and 0.09 g/mL. This study highlights the potential of Q. ilex extract as a safe and effective therapeutic strategy against HPV16- associated lesions in transgenic mouse models. The limitation of our study was the durability of transgenic animals. As a more sensitive species, we must always be careful with the durability of the test. We intend to study concentrations of 0.06 and 0.09 g/mL for longer to further investigate their possible effects.
- Histological lesions in hpv16-transgenic model: the effect of hidroethanolic extract of Lavandula pedunculata (mill.) Cav.Publication . Ferreira, Tiago; Nascimento-Gonçalves, Elisabete; Moutinho, Magda S.S.; Pires, Maria João; Bastos, Margarida M.S.M.; Medeiros, Rui; Nogueira, António José M.; Barros, Lillian; Ferreira, Isabel C.F.R.; Costa, Rui Miguel Gil; Rosa, Eduardo; Oliveira, Paula A.The K14HPV16 mice is a skin squamous carcinoma model that can be used to test antitumoral properties of several chemical and natural compounds1. Lavandula penduculata (Mill.) Cav., known as lavender, belongs to the Laminaceae family and has been used in traditional medicine as infusions to treat several conditions2. This work aimed to evaluate the effects of the hydroethanolic French lavender extract (FLE) in an HPV16-transgenic mice model lesions. The extract was obtained through a maceration with ethanol/water (80:20, v/v) and its phenolic composition was determined by HPLC-DADESI/ MS. The FLE was dissolved in drinking water at 6.8 mg/10mL/animal and the animals were supplemented during 29 consecutive days. Twentyeight male mice were randomly divided into four groups: (n=7/group): group I (HPV16- control); II (HPV16- FLE); III (HPV16+ control) and IV (HPV16+ FLE). After 29 days all animals were sacrificed by xylazineketamine overdose following cardiac puncture to obtain blood samples. Skin samples (chest and ear), kidney, liver and spleen were processed for histological analysis.A total of thirteen compounds were identified in the hydroethanolic extract, being salvianolic acid B and rosmarinic acid the main molecules present. Moreover, the compounds revealed to be stable in the drinking water for 5 days. Histological analyses of skin samples from wild-type mice exposed (group II) and not exposed (group I) to FLE showed normal skin histology. Group III showed skin chest epidermal hyperplasia in 100% of the mice while group IV showed less epidermal hyperplasia frequency (66.6%) (p>0.05). Concerning to liver, kidney, and spleen lesions there are no differences between groups (p>0.05). The lavender extract did not prevent the progression of HPV-16 induced cutaneous lesions in this model. These data deserve more investigation to clarify the effect of lavender extract on HPV-16 lesions.